The long-term goal of this project is to understand the brain preparatory states and processes which bias whether a given environmental event will be perceived or responded to. Spatial attention was selected as a model system for exploring preparatory set because it fosters a convergence of psychology and neurophysiology in both humans and animals. The proposed work will contribute to an understanding of the role of inhibitory mechanisms in integrating voluntary and reflexive visual orienting to provide a coherent continuity of visual experience and of visually guided behavior in humans. The experiments will examine the effects of saccade preparation on two inhibitory phenomena operative in regulating visual orienting, inhibition of return (IOR) and the fixation offset effect (FOE), and they will define the role of fronto-collicular circuits in mediating the effects of saccade preparation. They will measure the effect of preparatory precues on detecting and responding to visual signals in normal individuals and neurological patients with chronic, unilateral brain lesions involving the dorsolateral prefrontal cortex, the posterior association cortex and hemianopic patients with striate cortex lesions. The experiments will: 1) identify the cortical substrates for location-based and object-based IOR activated by exogenous visual signals; 2) determine whether endogenously generated IOR affects location-based, or object-based representations; 3) define the role of the frontal eye fields in the endogenous generation of IOR by saccade preparation; 4) investigate the effect of saccade preparation on the FOE for saccades toward and away from visual target signals and; 5) define the role of fronto-collicular circuits in mediating saccade preparation effects on the FOE.